This Mentored Patient-Oriented Research Career Development Award (K23) will provide Dr. Timothy D. Girard the opportunity to develop his career as a clinical investigator in the field of geriatric critical care and to establish an independent program of aging research focused on the clinical and molecular epidemiology of critical-illness associated cognitive impairment. Through an integrated program of didactic activities and course work in geriatrics, clinical and molecular epidemiology, and neuropsychology;intensive mentorship by local experts;and hands-on experience in the design, implementation, and analysis of a prospective clinical investigation, Dr. Girard will use this award to become a highly trained investigator in aging research. The primary scientific goal of this proposal is to identify and study the clinical and molecular predictors of long-term cognitive impairment (LTCI) after critical illness. Older patients account for the majority of ICU admissions, and cognitive impairment is a major impediment to meaningful recovery in this vulnerable population;survivors of critical illness have a 25%-75% risk of developing LTCI, a manifestation of persistent brain dysfunction associated with reduced quality of life and significant societal costs. Utilizing a prospective cohort investigation, Dr. Girard will identify those ICU patients at highest risk for LTCI and quantify the contribution of important risk factors to LTCI after critical illness. Specifically, the candidate will identify clinical risk factors for an increased incidence and severity of long-term cognitive impairment after critical illness (Aim 1). Furthermore, he will determine whether inflammation and coagulopathy are risk factors for an increased incidence and severity of LTCI after critical illness (Aim 2). Finally, Dr. Girard will determine which categories of delirium defined by clinical risk factors in critically ill patients are associated with an increased incidence and severity of LTCI after critical illness (Aim 3). This work will pave the way for the study of preventive and therapeutic interventions by ensuring that such efforts will be focused on patients at highest risk. Dr. Girard's long-term research goal is to improve the outcomes of older critically ill patients through the prevention and treatment of critical illness-associated cognitive impairment. RELEVANCE: Advances in intensive care medicine have improved the likelihood of survival for patients with critical illness, but studies have shown that many survivors develop persistent cognitive impairment, which reduces quality of life. This study seeks to identify risk factors for cognitive impairment after critical illness in order to guide the development of strategies to prevent and treat this potentially devastating complication of critical illness.